Insulin prodrugs hydrolyzable in vivo to yield peglylated insulin
원문보기
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
A61K-038/28
C07K-014/62
C07K-014/435
출원번호
US-0018879
(2000-06-19)
국제출원번호
PCT/US00/016879
(2000-06-19)
§371/§102 date
20020805
(20020805)
국제공개번호
WO00/078302
(2000-12-28)
발명자
/ 주소
Ekwuribe,Nnochiri N.
Ramaswamy,Muthukumar
Rajagopalan,Jayanthi
출원인 / 주소
Biocon Limited
대리인 / 주소
Moore & Van Allen PLLC
인용정보
피인용 횟수 :
0인용 특허 :
147
초록▼
The present invention relates generally to hydrolyzable drug-oligomer conjugates, pharmaceutical compositions comprising such conjugates, and to methods for making and using such conjugates and pharmaceutical compositions. For example, a conjugate of insulin, PEG, and oleic acid can be orally admini
The present invention relates generally to hydrolyzable drug-oligomer conjugates, pharmaceutical compositions comprising such conjugates, and to methods for making and using such conjugates and pharmaceutical compositions. For example, a conjugate of insulin, PEG, and oleic acid can be orally administered.
대표청구항▼
We claim: 1. A drug-oligomer conjugate having the following general formula: description="In-line Formulae" end="lead"D--[(H--H'q)--Lo]p (Formula 10) description="In-line Formulae" end="tail" wherein D is insulin or a functional equivalent thereof; H is a PEG polymer having from 1 to 10 PEG un
We claim: 1. A drug-oligomer conjugate having the following general formula: description="In-line Formulae" end="lead"D--[(H--H'q)--Lo]p (Formula 10) description="In-line Formulae" end="tail" wherein D is insulin or a functional equivalent thereof; H is a PEG polymer having from 1 to 10 PEG units; H' is a hydrophilic moiety; L is a lipophilic moiety; the H--H' bond is hydrolyzable; q is a number from 1 to the maximum number of covalent bonding sites at which H' can form a bond with H; o is a number from 1 to the maximum number of covalent bonding sites at which L can form a bond with H'; and p is a number from 1 to the maximum number of covalent bonding sites at which--[(H--H'q)--Lo] can form a bond with D. 2. The drug-oligomer conjugate of claim 1, wherein H, H' and L are selected and arranged such that the drug-oligomer conjugate is amphiphilic. 3. The drug-oligomer conjugate of claim 1, wherein H is a PEG polymer having from 2 to 8 PEG units. 4. The drug-oligomer conjugate of claim 1, wherein H is a PEG polymer having from 2 to 7 PEG units. 5. The drug-oligomer conjugate of claim 1, wherein H is a PEG polymer having 3 PEG units. 6. The drug-oligomer conjugate of claim 1, wherein H is a PEG polymer having 4 PEG units. 7. The drug-oligomer conjugate of claim 1, wherein H is a PEG polymer having 5 PEG units. 8. The drug-oligomer conjugate of claim 1, wherein H is a PEG polymer having 6 PEG units. 9. The drug-oligomer conjugate of claim 1, wherein H' is a hydrophilic moiety selected from the group consisting of straight or branched PEG polymers and sugars. 10. The drug-oligomer conjugate of claim 1, wherein H' is a straight PEG polymer. 11. The drug-oligomer conjugate of claim 10, wherein the PEG polymer has from 1 to 130 PEG units. 12. The drug-oligomer conjugate of claim 10, wherein the PEG polymer has from 1 to 100 PEG units. 13. The drug-oligomer conjugate of claim 1, wherein L is a lipophilic moiety selected from the group consisting of alkyl moieties, cholesterol, and fatty acid moieties. 14. The drug-oligomer conjugate of claim 1, wherein L is an alkyl moiety. 15. The drug-oligomer conjugate of claim 1, wherein L is cholesterol. 16. The drug-oligomer conjugate of claim 1, wherein L is a fatty acid moiety. 17. The drug-oligomer conjugate of claim 16, wherein the fatty acid moiety has between 2 and 28 carbon atoms. 18. The drug-oligomer conjugate of claim 16, wherein the fatty acid moiety has between 12 and 22 carbon atoms. 19. The drug-oligomer conjugate of claim 1, wherein D is insulin or insulin lispro. 20. The drug-oligomer conjugate of claim 1, wherein the H'--L bond is non-hydrolyzable. 21. The drug-oligomer conjugate of claim 1, wherein H' and L are present as a component H'--L having the formula CH3(CH 2)n(OC2H4)mOH (Formula 3), wherein n=3 to 25 and m=1 to 7. 22. The drug-oligomer conjugate of claim 1, wherein H' and L are present as a component H'--L having the formula CH3(CH 2)n(OC2H4)mOCH2CO 2H (Formula 4), wherein n=3 to 25 and m=1 to 6. 23. The drug-oligomer conjugate of claim 1, wherein H' and L are present as a component H'--L having the formula R--(OC2H 4)mCH2CO2H (Formula 6), wherein m=0 to 5 and R=cholesterol or adamantane. 24. The drug-oligomer conjugate of claim 1, wherein H' and L are present as a component H'--L having the formula CH3(CH 2--CH═CH)6(CH2)2CH2(OC 2H4)mOH (Formula 8), wherein m=1 to 7. 25. The drug-oligomer conjugate of claim 1, wherein H' and L are present as a component H'--L having the formula CH3(CH 2--CH═CH)6(CH2)2CX(OC2H 4)mOH (Formula 9), wherein m=1 to 7.
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이 특허에 인용된 특허 (147)
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